Structural analysis of H-2Kf and H-2Kfm1 by using H-2K locus-specific sequences

Robert M. Horton, William H. Hildebrand, John M. Martinko, Larry R Pease

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The H-2Kf allele and the spontaneous mutant Kfm1 have been cloned using locus-specific sequences. The mutation consists of a cluster of four nucleotide changes, resulting in amino acid substitutions at positions 95 (Leu→Ile) and 97 (Val→Arg). This finding has structural, genetic, and technical implications. The amino acid substitutions are located on the β-strands of the antigen recognition site. Their influence on the allogeneic properties of the Kf glycoprotein is consistent with the hypothesis that alloreactivity results from alterations in the spectrum of peptides presented to T cells. These substitutions would not, however, be predicted to be directly accessable for binding to antibodies. Nonetheless, the fm1 mutant binds anti Kf alloantisera and mAb much less strongly than the parent molecule, suggesting some indirect effect of these residues on serologic phenotype. The mutant is also interesting genetically because the sequence of the mutated region is identical to the sequence of the Df gene. This implies that there is a gene conversion-like mutational mechanism operating in the H-2f haplotype. Finally, the strategy used to obtain these K-locus cDNA should prove generally useful for isolating other MHC alleles.

Original languageEnglish (US)
Pages (from-to)1782-1787
Number of pages6
JournalJournal of Immunology
Volume145
Issue number6
StatePublished - Sep 15 1990

Fingerprint

Amino Acid Substitution
Alleles
Gene Conversion
Haplotypes
Glycoproteins
Nucleotides
Complementary DNA
T-Lymphocytes
Phenotype
Antigens
Peptides
Mutation
Antibodies
Genes

ASJC Scopus subject areas

  • Immunology

Cite this

Horton, R. M., Hildebrand, W. H., Martinko, J. M., & Pease, L. R. (1990). Structural analysis of H-2Kf and H-2Kfm1 by using H-2K locus-specific sequences. Journal of Immunology, 145(6), 1782-1787.

Structural analysis of H-2Kf and H-2Kfm1 by using H-2K locus-specific sequences. / Horton, Robert M.; Hildebrand, William H.; Martinko, John M.; Pease, Larry R.

In: Journal of Immunology, Vol. 145, No. 6, 15.09.1990, p. 1782-1787.

Research output: Contribution to journalArticle

Horton, RM, Hildebrand, WH, Martinko, JM & Pease, LR 1990, 'Structural analysis of H-2Kf and H-2Kfm1 by using H-2K locus-specific sequences', Journal of Immunology, vol. 145, no. 6, pp. 1782-1787.
Horton, Robert M. ; Hildebrand, William H. ; Martinko, John M. ; Pease, Larry R. / Structural analysis of H-2Kf and H-2Kfm1 by using H-2K locus-specific sequences. In: Journal of Immunology. 1990 ; Vol. 145, No. 6. pp. 1782-1787.
@article{9c7cf735682d4c608bc3b33c972197fd,
title = "Structural analysis of H-2Kf and H-2Kfm1 by using H-2K locus-specific sequences",
abstract = "The H-2Kf allele and the spontaneous mutant Kfm1 have been cloned using locus-specific sequences. The mutation consists of a cluster of four nucleotide changes, resulting in amino acid substitutions at positions 95 (Leu→Ile) and 97 (Val→Arg). This finding has structural, genetic, and technical implications. The amino acid substitutions are located on the β-strands of the antigen recognition site. Their influence on the allogeneic properties of the Kf glycoprotein is consistent with the hypothesis that alloreactivity results from alterations in the spectrum of peptides presented to T cells. These substitutions would not, however, be predicted to be directly accessable for binding to antibodies. Nonetheless, the fm1 mutant binds anti Kf alloantisera and mAb much less strongly than the parent molecule, suggesting some indirect effect of these residues on serologic phenotype. The mutant is also interesting genetically because the sequence of the mutated region is identical to the sequence of the Df gene. This implies that there is a gene conversion-like mutational mechanism operating in the H-2f haplotype. Finally, the strategy used to obtain these K-locus cDNA should prove generally useful for isolating other MHC alleles.",
author = "Horton, {Robert M.} and Hildebrand, {William H.} and Martinko, {John M.} and Pease, {Larry R}",
year = "1990",
month = "9",
day = "15",
language = "English (US)",
volume = "145",
pages = "1782--1787",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "6",

}

TY - JOUR

T1 - Structural analysis of H-2Kf and H-2Kfm1 by using H-2K locus-specific sequences

AU - Horton, Robert M.

AU - Hildebrand, William H.

AU - Martinko, John M.

AU - Pease, Larry R

PY - 1990/9/15

Y1 - 1990/9/15

N2 - The H-2Kf allele and the spontaneous mutant Kfm1 have been cloned using locus-specific sequences. The mutation consists of a cluster of four nucleotide changes, resulting in amino acid substitutions at positions 95 (Leu→Ile) and 97 (Val→Arg). This finding has structural, genetic, and technical implications. The amino acid substitutions are located on the β-strands of the antigen recognition site. Their influence on the allogeneic properties of the Kf glycoprotein is consistent with the hypothesis that alloreactivity results from alterations in the spectrum of peptides presented to T cells. These substitutions would not, however, be predicted to be directly accessable for binding to antibodies. Nonetheless, the fm1 mutant binds anti Kf alloantisera and mAb much less strongly than the parent molecule, suggesting some indirect effect of these residues on serologic phenotype. The mutant is also interesting genetically because the sequence of the mutated region is identical to the sequence of the Df gene. This implies that there is a gene conversion-like mutational mechanism operating in the H-2f haplotype. Finally, the strategy used to obtain these K-locus cDNA should prove generally useful for isolating other MHC alleles.

AB - The H-2Kf allele and the spontaneous mutant Kfm1 have been cloned using locus-specific sequences. The mutation consists of a cluster of four nucleotide changes, resulting in amino acid substitutions at positions 95 (Leu→Ile) and 97 (Val→Arg). This finding has structural, genetic, and technical implications. The amino acid substitutions are located on the β-strands of the antigen recognition site. Their influence on the allogeneic properties of the Kf glycoprotein is consistent with the hypothesis that alloreactivity results from alterations in the spectrum of peptides presented to T cells. These substitutions would not, however, be predicted to be directly accessable for binding to antibodies. Nonetheless, the fm1 mutant binds anti Kf alloantisera and mAb much less strongly than the parent molecule, suggesting some indirect effect of these residues on serologic phenotype. The mutant is also interesting genetically because the sequence of the mutated region is identical to the sequence of the Df gene. This implies that there is a gene conversion-like mutational mechanism operating in the H-2f haplotype. Finally, the strategy used to obtain these K-locus cDNA should prove generally useful for isolating other MHC alleles.

UR - http://www.scopus.com/inward/record.url?scp=0025173553&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025173553&partnerID=8YFLogxK

M3 - Article

VL - 145

SP - 1782

EP - 1787

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 6

ER -